Abstract:
:More than 90% of patients with severe congenital neutropenia (SCN) respond to granulocyte colony-stimulating factor (G-CSF) therapy. The basis for the refractory state in the remaining patients is unknown. To address this issue, we studied a child with SCN who was totally unresponsive to G-CSF and had a novel point mutation in the extracellular domain of the G-CSF receptor (GCSF-R). Marrow stromal support of granulopoiesis was evaluated by plating CD34(+) cells on preformed stromal layers. Nonadherent cells were harvested and assayed in clonogenic assays for granulocytic colony production. The in vitro effect of G-CSF and corticosteroids on granulopoiesis was evaluated in clonogenic assays of marrow mononuclear cells, by proliferation studies of the murine myeloid cell line 32D expressing the patient's mutated G-CSFR, and by measuring STAT5 activation in nuclear extracts from stimulated cells.Patient's stroma supported granulopoiesis derived from control marrow CD34(+) cells in a normal manner. Normal stroma, however, failed to induce granulopoiesis from patient's CD34(+) cells. Clonogenic assays of the patient's marrow mononuclear cells incorporating either G-CSF or hydrocortisone produced little neutrophil growth. In contrast, inclusion of both G-CSF and hydrocortisone in the cytokine "cocktail" markedly increased the neutrophil numbers. Proliferation of 32D cells expressing the mutated receptor and STAT5 activation were improved by a combination of G-CSF and dexamethasone. When small daily doses of oral prednisone were then administered to the patient with conventional doses of subcutaneous G-CSF, the patient responded with increased neutrophil numbers and with a complete reversal of the infectious problems. These data provide insight into SCN unresponsive to standard G-CSF treatment and to the potential corrective action of combined treatment with G-CSF and corticosteroids through synergistic activation of STAT5.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Dror Y,Ward AC,Touw IP,Freedman MHdoi
10.1016/s0301-472x(00)00544-0keywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
1381-9issue
12eissn
0301-472Xissn
1873-2399pii
S0301-472X(00)00544-0journal_volume
28pub_type
杂志文章abstract::We have previously shown that CD33- CD34+ human marrow cells are capable of giving rise to colony-forming cells (CFC) in long-term marrow culture (LTMC) but are mainly depleted of progenitors that directly form colonies in semi-solid media. In contrast, the CD33+ CD34+ population contains most of the CFC but not the p...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high-performance liquid chromatography similarly to purified human erythropoietin (Ep) ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00778-0
更新日期:2002-02-01 00:00:00
abstract::High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract:OBJECTIVE:The primary objective of this study was to identify and clone the first nonmammalian thrombopoietin (TPO), chicken TPO, and its receptor c-Mpl for the purpose of characterizing their activities both in vitro and in vivo. MATERIALS AND METHODS:Chicken TPO was cloned using the methods of reverse transcriptase ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.12.001
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVES:To identify the regulatory sequences driving Gata1 expression in conventional dendritic cells (cDC). MATERIALS AND METHODS:The number and expression levels of Gata1, Gata1-target genes and hypersensitive site (HS) 2 (the eosinophil-specific enhancer)-driven green fluorescent protein (GFP) reporter of cDCs f...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.006
更新日期:2010-06-01 00:00:00
abstract::Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and norma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential h...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::In a selective culture system, the in vitro generation of terminal deoxynucleotidyl transferase positive (TdT+) B cell progenitors from rat, mouse, and human bone marrow (BM) is characterized by initial lymphoid colonization of a mouse BM feeder layer. In the present study, four sequentially appearing subsets of B cel...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract:OBJECTIVE:Using transplantation of a clonal population of cells derived from a single hematopoietic stem cell (HSC) of transgenic enhanced green fluorescent protein (EGFP) mice, we have documented the hematopoietic origin of myofibroblasts, such as kidney mesangial cells and brain microglial cells. Because myofibroblas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.10.008
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:The evolutionarily conserved Kit receptor is vital for function of hematopoietic stem cells (HSC). Kit(W-41) (W-41) and Kit(W-42) (W-42) are single residue changes in the KIT intracellular phosphotransferase domain, while Kit(W-v) (W-v) is a single residue change in the ATP binding domain. This study tests ho...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.10.001
更新日期:2007-02-01 00:00:00
abstract::Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DN...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion mo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00031-9
更新日期:1999-02-01 00:00:00
abstract::The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract:OBJECTIVE:Excessive apoptosis may have a role in the ineffective hematopoiesis and cytopenias observed in myelodysplastic syndromes. The goals of this study were 1) to quantify apoptosis in patients with "early stage" myelodysplasia [including patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), RA...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00179-x
更新日期:2000-07-01 00:00:00
abstract:OBJECTIVE:The retinoic acid receptors (RARs) alpha, beta2, and gamma regulate specific subsets of target genes during all-trans retinoic acid (RA) induced differentiation of F9 teratocarcinoma stem cells. The Tie1 gene exhibited reduced expression in RA-treated F9 RARgamma-/- cells as compared to wild-type (WT) by micr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.12.016
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVE:We previously demonstrated the presence of nucleoside diphosphate kinase NDPK/NM23 in normal human plasma. It also was reported that extracellular NM23 could inhibit differentiation of certain hematopoietic cell lines. We further investigated the extracellular effect of NM23 on hematopoiesis by adding recombi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00809-3
更新日期:2002-07-01 00:00:00
abstract:OBJECTIVE:The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00237-6
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:A multi-step statistical strategy was applied to quantify individual and interactive effects of cytokines on megakaryopoiesis and to determine the concentration of the selected cytokines that optimize ex vivo megakaryocyte (MK) expansion, maturation, and platelet production in stromal- and serum-free conditio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.06.020
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:In comparison with stem cell transplantation using bone marrow or cytokine-mobilized peripheral blood, cord blood transplantation is characterized by delayed engraftment, in particular platelet recovery. The differences in the kinetics of engraftment may be related to quantitative differences in the numbers o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00004-3
更新日期:2003-04-01 00:00:00
abstract::The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morpholo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract:OBJECTIVES:GPIIb integrin expression has been found on platelets and megakaryocytes, and more recently on immature hematopoietic progenitors. We set out to investigate expression of GPIIb in other hematopoietic cell lineages and, having detected it on mast cells, aimed to determine what possible role it might perform. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.01.011
更新日期:2005-04-01 00:00:00
abstract::A functional method for estimation of plasminogen activator (PA) activity is described. The end-point method follows the PA-dependent conversion of the inactive plasminogen to the potent protease plasmin. The formation of plasmin is monitored by its activity on 14C-globin to form acid-soluble radioactive products. The...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::It has been shown that in xenotransplantation of human cells into immunodeficient mice, the mouse strain background is critical. For example, the nonobese diabetic (NOD) strain is most efficient, the BALB/c is moderate, and the C57BL/6 is inefficient for human cell engraftment. We have shown that the NOD-specific poly...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.11.005
更新日期:2014-03-01 00:00:00
abstract::Hematopoietic progenitor cells (low density, lineage negative [Lin-], depleted of CD4+, CD8+, B220+, Gr-1+, Mac-1+, CD71+, and Thy1.2+ cells) can engraft lethally irradiated mice when transplanted within, but not across the major histocompatibility (MHC) antigen barrier. We hypothesized that our progenitor cell prepar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult A...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.02.010
更新日期:2016-06-01 00:00:00
abstract::The prototypic human acute phase reactant, C-reactive protein (CRP), and a structurally modified form of CRP (mCRP) were studied as agents which could stimulate thrombopoiesis in both in vitro and in vivo mouse models. mCRP, but not the widely studied (native) pentameric form of CRP, demonstrated significant megakaryo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS:Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00137-5
更新日期:2000-05-01 00:00:00